IDSA: Vancomycin Outdoes Flagyl in Severe C. difficile Diarrhea

Action Points

Note that this randomized controlled trial found that for severe cases of diarrhea associated with Clostridium difficile infection, vancomycin, not Flagyl (metronidazole), had a higher cure rate.

Advise patients who ask that new strains of C. difficile have recently been identified that cause more aggressive and dangerous disease.

This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

TORONTO, Oct. 13 -- For severe cases of diarrhea associated with Clostridium difficile infection, vancomycin should be the first line of treatment, researchers said here.

In a randomized, double-blind, head-to-head trial against Flagyl (metronidazole) -- the typical first-line therapy -- vancomycin did significantly better in severe cases, Melinda Davis, M.D., of the University of Illinois at Chicago reported at the Infectious Diseases Society of America meeting.

"If they were considered severe, there was a much higher cure rate with vancomycin," Dr. Davis said, but when the cases were classified as mild, the two drugs were equivalent.

In the prospective placebo-controlled trial, 172 patients were randomized to 125 mg of liquid vancomycin and a placebo tablet or a 250 mg tablet of Flagyl and placebo liquid. Patients received the medication daily for 10 days. The placebos were given for blinding purposes.

Of the 172 patients enrolled, 22 did not complete the trial for various reasons, including non-compliance and loss to follow-up. Also, eight patients died before three days of therapy had been completed.

Of the 150 patients who completed the trial, Dr. Davis said, 81 were classed as mild and 69 as having severe diarrhea. Patients were put in the severe category if they had pseudomembranous colitis, were in the intensive care unit because of the diarrhea, or if they had any two of fever, a high white blood cell count, age more than 60, or low albumin.

The study found that in severe cases, the cure rate for vancomycin was 97%, while Flagyl cured only 76%. The difference was statistically significant at P=0.02. Relapse was seen in 3/30 (10%) with vancomycin and six of 29 (21%) with Flagyl (P=0.30).

Of 81 with mild disease, the cure rates were 39 of 40 (98%) with vancomycin and 37 of 41 (90%) with Flagyl (P=0.36). There were relapses for two of 39 (5%) with vancomycin and three of 37 (8%) with Flagyl (P=0.67).

A cure was defined as resolution of the diarrhea within six days and sustained through day 10 of treatment, Dr. Davis said.

The study was carried out between 1994 and 2002, Dr. Davis said, before the recent emergence of highly aggressive and virulent strains of C. difficile. "The new strains do cause more severe disease," she said, which would suggest than vancomycin might be indicated.

The value of the study is that it is a randomized controlled trial that supports a growing consensus about what medications to use in the increasing number of severe C. difficile cases, commented L. Clifford McDonald, M.D., a CDC medical in Atlanta.

"There haven't been enough randomized controlled trials in this area," Dr. McDonald said in an interview. "We need more of them."

In fact, only two earlier prospective trials of Flagyl versus vancomycin have been carried out, Dr. Davis said, and neither was blinded nor stratified patients by severity of C. difficile-associated diarrhea.

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